TY - JOUR

T1 - Key risk factors of asthma-like symptoms are mediated through infection burden in early childhood

AU - Kyvsgaard, Julie Nyholm

AU - Brustad, Nicklas

AU - Hesselberg, Laura Marie

AU - Vahman, Nilo

AU - Thorsen, Jonathan

AU - Schoos, Ann Marie Malby

AU - Bønnelykke, Klaus

AU - Stokholm, Jakob

AU - Chawes, Bo Lund

N1 - Publisher Copyright: © 2023 The Authors

PY - 2024

Y1 - 2024

N2 - Background: Risk factors of asthma-like symptoms in childhood may act through an increased infection burden because infections often trigger these symptoms. Objective: We sought to investigate whether the effect of established risk factors of asthma-like episodes in early childhood is mediated through burden and subtypes of common infections. Methods: The study included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort, in which infections were registered prospectively in daily diaries from age 0 to 3 years. The association between established risk factors of asthma-like episodes and infection burden was analyzed by quasi-Poisson regressions, and mediation analyses were performed for significant risk factors. Results: In the first 3 years of life, the children experienced a median of 16 (interquartile range, 12-23) infectious episodes. We found that the infection burden significantly (PACME <.05) mediated the association of maternal asthma (36.6% mediated), antibiotics during pregnancy (47.3%), siblings at birth (57.7%), an asthma exacerbation polygenic risk score (30.6%), and a bacterial airway immune score (80.2%) with number of asthma-like episodes, whereas the higher number of episodes from male sex, low birth weight, low gestational age, and maternal antibiotic use after birth was not mediated through an increased infection burden. Subtypes of infections driving the mediation were primarily colds, pneumonia, gastroenteritis, and fever, but not acute otitis media or acute tonsillitis. Conclusions: Several risk factors of asthma-like symptoms in early childhood act through an increased infection burden in the first 3 years of life. Prevention of infectious episodes may therefore be beneficial to reduce the burden of asthma-like symptoms in early childhood.

AB - Background: Risk factors of asthma-like symptoms in childhood may act through an increased infection burden because infections often trigger these symptoms. Objective: We sought to investigate whether the effect of established risk factors of asthma-like episodes in early childhood is mediated through burden and subtypes of common infections. Methods: The study included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort, in which infections were registered prospectively in daily diaries from age 0 to 3 years. The association between established risk factors of asthma-like episodes and infection burden was analyzed by quasi-Poisson regressions, and mediation analyses were performed for significant risk factors. Results: In the first 3 years of life, the children experienced a median of 16 (interquartile range, 12-23) infectious episodes. We found that the infection burden significantly (PACME <.05) mediated the association of maternal asthma (36.6% mediated), antibiotics during pregnancy (47.3%), siblings at birth (57.7%), an asthma exacerbation polygenic risk score (30.6%), and a bacterial airway immune score (80.2%) with number of asthma-like episodes, whereas the higher number of episodes from male sex, low birth weight, low gestational age, and maternal antibiotic use after birth was not mediated through an increased infection burden. Subtypes of infections driving the mediation were primarily colds, pneumonia, gastroenteritis, and fever, but not acute otitis media or acute tonsillitis. Conclusions: Several risk factors of asthma-like symptoms in early childhood act through an increased infection burden in the first 3 years of life. Prevention of infectious episodes may therefore be beneficial to reduce the burden of asthma-like symptoms in early childhood.

KW - cough

KW - dyspnea

KW - infant

KW - infection

KW - mediation analysis

KW - preschool child

KW - Respiratory signs and symptoms

KW - risk factors

KW - wheezing

U2 - 10.1016/j.jaci.2023.11.019

DO - 10.1016/j.jaci.2023.11.019

M3 - Journal article

C2 - 37995855

AN - SCOPUS:85181454138

VL - 153

SP - 684

EP - 694

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -